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Exploration of three-dimensional structural space has become crucial for the development of novel bioactive molecules. In this context, polar spirocycles have emerged as key scaffolds due to their enhanced 3D character and well-defined spatial orientation. Herein, we report the development of a highly modular strategy to access beta-spirocyclic pyrrolidine derivatives from readily available starting materials, i.e., cyclic ketones and amino or oxamic acids. The sequence proceeds through a straightforward Knoevenagel condensation, followed by a domino Giese-type reaction/base-mediated cyclisation process, delivering a broad scope of polar spirocyclic scaffolds in good to excellent yields. The products can be readily diversified to access a wider range of spirocyclic cores (such as lactams or succinimides), thus increasing the versatility of our method to gain rapid access to libraries of potential drug-like molecules.

Due to its role in lipid biosynthesis, choline kinase α1 (CKα1) is an interesting target for the development of new antitumor agents. In this work, we present a series of 41 compounds designed based on the well-known and successful strategy of introducing thienopyridine and pyrimidine as bioisosteres of other heterocycles in active antitumor compounds. Notwithstanding the fact that some of these compounds do not show significant enzymatic inhibition, others, in contrast, feature substantially improved enzymatic and antiproliferative inhibition values. This is also confirmed by docking analysis, whereby compounds with longer linkers and thienopyrimidine cationic head have been identified as the most compelling. Among the best compounds is Ff-35, which inhibits the growth of different tumor cells at submicromolar concentrations. Moreover, Ff-35 is more potent in inhibiting CKα1 than other previous biscationic derivatives. Treatment of A549, Hela, and MDA-MB-231 cells with Ff-35 results in their arrest at the G1 phase of the cell cycle. Furthermore, the compound induces cellular apoptosis in a concentration-dependent manner. Altogether, these findings indicate that Ff-35 is a promising new chemotherapeutic agent with encouraging preclinical potential.

The purpose of this study is to guide pricing policies of Airbnb accommodation rentals to reduce inefficient pricing strategies through a novel application of topic modelling and a fuzzy clustering. In particular, the method proposes the application of Structural Topic Modelling, which explains a set of observations from latent topics. The associations between topics by Fuzzy C-Means Clustering are analysed to obtain new, more compact representations of topics (i.e., metatopics). This research identifies 15-metatopics related to Airbnb accommodations based on location and connectivity, enjoyment of domestic and everyday services, and the possibility of more authentic local experiences, among others. The influence of key metatopics on the price of Airbnb accommodations is determined by applying Extreme Gradient Boosting (an efficient and scalable implementation of gradient boosting framework) and Shapley Additive Explanations values. To sum up, our research provides an explicit contribution of user-generated content to promote the development of mutually beneficial relationships between guests and hosts, and detects future lines of research and practical and conceptual implications of the findings.